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Drosophila melanogaster transcriptional response to Nora virus infection
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). (Dan Hultmark)
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Institute of Biomedical technology, University of Tampere, Tampere, Finland.ORCID-id: 0009-0005-2590-7324
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Institute of Biomedical technology, University of Tampere, Tampere, Finland.ORCID-id: 0000-0002-6506-5855
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Abstract [en]

Pathogens induce the activation and suppression of several genes, including potent immune response genes in Drosophila melanogaster. Although several different immune response pathways have been shown to play important roles in the defense against viruses, most of these responses are virus-specific and there appears to be no pathway or set of genes that are induced in response to all viruses. We have here identified genes that are differentially expressed in Drosophila melanogaster in response to Nora virus infection. Our results indicate that none of the known immune response pathways are induced following Nora virus infection, but among the upregulated genes we find three members of the same family as CHKov1 and CHKov2 (ref(3)D), which are involved in resistance to the σ virus. Although Nora virus is a known target of the RNAi pathway, none of the genes belonging to this antiviral system were affected. On the contrary, known immunity responders, such as targets of the Toll and Imd pathways, were downregulated. Several heat-shock proteins, which are usually activated in response to external stimuli, are induced during Nora virus infection. Strikingly, several stress response genes, chaperones and genes required for repair were induced, while digestive enzymes and proteins involved in nutrient uptake and transport were shut down.

Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-127350OAI: oai:DiVA.org:umu-127350DiVA, id: diva2:1045375
Tillgänglig från: 2016-11-09 Skapad: 2016-11-09 Senast uppdaterad: 2026-05-05Bibliografiskt granskad
Ingår i avhandling
1. Biology of a small RNA virus that infects Drosophila melanogaster
Öppna denna publikation i ny flik eller fönster >>Biology of a small RNA virus that infects Drosophila melanogaster
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Drosophila melanogaster has been extensively used as a model organism to study diverse facets of biology, including host-pathogen interactions and the basic biology of its pathogens. I have used the fruit fly as a model to study elementary aspects of Nora virus biology, such as the role of the different proteins encoded by the virus genome. Nora virus, an enteric virus transmitted via the feca-oral route, does not cause any obvious pathology in the fly, although the infection is persistent. Nora virus genome consists of a positive strand RNA that is translated in four open reading frames (ORF).  Since sequence homology studies did not yield much information about the different Nora virus proteins, I have used the cDNA clone of the virus to construct mutants to identify the specific function of each protein. My results have shown that,

1) The protein(s) encoded by ORF 1 are crucial for the replication of the virus genome.

2) The C-terminus of the ORF 1-encoded protein (VP1), is an inhibitor to the RNAi pathway.

3) The transmembrane domain in the N-terminus of the ORF2-encoded protein (VP2) is important for the formation of Nora virus virions.

4) The ORF 3-encoded protein (VP3) forms α-helical trimers and this protein is essential for the stability of Nora virus capsid.                                                    

I have also performed RNA sequencing to investigate the transcriptional response of D. melanogaster in response to Nora virus infection and my results indicate that,                       

5) The upregulation of genes related to cellular stress and protein synthesis and the downregulation of basal digestive machinery, together with the induction of upd3, implies major gut epithelium damage and subsequent regeneration.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2016. s. 52
Nyckelord
Nora virus, Drosophila melanogaster, virus biology, host-pathogen interaction
Nationell ämneskategori
Cell- och molekylärbiologi
Forskningsämne
molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-127352 (URN)978-91-7601-593-3 (ISBN)
Disputation
2016-12-01, Hörsal 135, Byggnad 9A, Norrlands Universitetssjukhus, Umeå, 14:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2016-11-10 Skapad: 2016-11-09 Senast uppdaterad: 2025-02-10Bibliografiskt granskad

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Sadanandan, Sajna AnandEkström, Jens-OlaHultmark, Dan

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